Jeff Evans - Translational Cancer Therapeutics

Introduction

evans j

Current strategies in the development of new therapies for malignant disease are based on exploiting our increasing understanding of the molecular and cellular basis of cancer development and progression.

Work in our group is aimed at developing novel laboratory models that will allow us to understand the biological function of key tumour suppressor genes and oncogenes in vivo in both normal tissues and tumours, and that will allow us to identify and characterise the signalling pathways that are deregulated at the early stages of pancreatic cancer as well as during the development and progression of the invasive and metastatic phenotype.

Using these models, we will determine how potential anti-cancer agents might best be evaluated in subsequent clinical trials.

Lab Report

Key Publications

Olmos D, A'Hern R, Marsoni S, Tabernero J, Gomez-Roca C, Verweij J, Voest EE, Schöffski P, Ang JE, Penel N, Schellens JHM, Gianni L, Brunetto AT, Evans TRJ, Wilson R, Sessa C, Plummer RE, Morales R, Soria J-C, Kaye SB, on behalf of the European Drug Development Network (EDDN). Patient selection for oncology Phase I trials – a multi-institutional study of prognostic factors. Journal of Clinical Oncology 30: 996-1004, 2012

Morton JP, Timpson P, Karim SA, Ridgway RA, Athineos D, Doyle B, Jamieson NB, Oien KA, Lowy AM, Brunton VG, Frame MC, Evans TRJ, Sansom OJ. Mutant p53 drives metastasis and overcomes growth arrest/senescence in pancreatic cancer. Proc Natl Acad Sci USA 107: 246-251, 2010

Morton JP, Karim SA, Graham K, Timpson P, Jamieson NB, Athineos D, McKay CJ, Heung M-Y, Oien KA, Frame MC, Evans TRJ, Sansom OJ, Brunton VG. Dasatinib inhibits the development of metastases in a mouse model of pancreatic ductal adenocarcinoma. Gastroenterology 139: 292-303, 2010

Biography

Education and qualifications

2014: FRCP (Edinburgh)
2000: FRCP (London)
1998: FRCP (Glasgow)
1993: MD, University of London
1988: MRCP (UK)
1984: MB BS, St Bartholomew's Hospital, University of London

Appointments

2012-present: Director, Institute of Cancer Sciences, University of Glasgow (Acting Director from November 2011)
2011-present: Lead, Glasgow Experimental Cancer Medicine Centre (ECMC)
2010-present: Head, Experimental Cancer Therapeutics Unit, University of Glasgow
2007-present: Honorary Group Leader, CRUK Beatson Institute
2007-2010: Deputy Head, Division of Cancer Sciences & Molecular Pathology, University of Glasgow
2005-present: Professor of Translational Cancer Research (University of Glasgow); Honorary Consultant Medical Oncology (Beatson West of Scotland Cancer Centre, Glasgow)
1996-2005: Senior Lecturer and Honorary Consultant in Medical Oncology, Centre for Oncology & Applied Pharmacology, University of Glasgow; Beatson Oncology Centre, Glasgow
1991-1996: Lecturer/Honorary Senior Registrar in Medical Oncology, St George's Hospital Medical School, London
1989-1991: Research Fellow in Medical Oncology, St George's Hospital Medical School and Charing Cross Hospital Medical School, University of London; Institute of Cancer Research, Sutton, Surrey

Current committee membership

ECMC-Industry Combinations Alliance Joint Steering Committee
NCRI Upper GI Cancer Clinical Studies Group and Pancreatic Cancer and Gastro-oesophageal Cancer sub-groups
Chair, Wales Clinical Trials Unit Independent Data Monitoring Committee
Faculty 1000 Oncology Evaluation Board – Oncology Agents Section
All Ireland Cooperative Oncology Group Panel of international peer reviewers
Editorial Board, British Journal of Cancer (Co-Editor - Clinical Subjects)
Editorial Board, BMC Cancer

Recent Publications

2018

Cook N, Basu B, Smith D-M, Gopinathan A, Evans TRJ, Steward WP, Palmer D, Propper D, Venugopal B, Hategan M, Anthoney DA, Hampson LV, Nebozhyn M, Tuveson D, Farmer-Hall H, Turner H, McLeod R, Halford S, Jodrell DA. Phase I trial of the ɣ-secretase inhibitor MK-0752 in combination with gemcitabine in patients with pancreatic ductal adenocarcinoma. Br J Cancer 2018 Feb 13. doi: 10.1038/bjc.2017.495. [Epub ahead of print]

Saito K, Kraljevic S, Tamai T, Ren M, Cheng, A-L. A randomised phase 3 trial of lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma. Lancet 2018 Feb 9. pii: S0140-6736(18)30207-1. doi: 10.1016/S0140-6736(18)30207-1. [Epub ahead of print]

Wilson RAM, Evans TRJ, Fraser AR, Nibbs RJB. Immune Checkpoint Inhibitors: New strategies to checkmate cancer. Clin Exp Immunol 2018; 191: 133-48

2017

Carotenuto P, Fassan M, Pandolfo R, Lampis A, Vicentini C, Cascione L, Paulus-Hock V, Boulter L, Guest R, Quagliata L, Hahne JC, Ridgway R, Jamieson T, Athineos D, Veronese A, Visone R, Murgia C, Ferrari G, Guzzardo V, Evans TRJ et al. Wnt signalling modulates transcribed-ultraconserved regions in hepatobiliary cancers. Gut 2017; 66: 1268-77

de la Cruz-Merino L, Di Guardo L, Grob J-J, Venosa A, Larkin J, McArthur GA, Ribas A, Ascierto PA, Evans TRJ, Gomez-Escobar A, Barteselli G, Eng S, Hsu JJ, Uyei A, Dréno B. Clinical features of serous retinopathy observed with cobimetinib in patients with BRAF-mutated melanoma treated in the randomized coBRIM study. J Transl Med 2017; 15: 146-54

Evans TRJ, Van Cutsem E, Moore MJ, Bazin IS, Rosemurgy A, Bodoky G, Deplanque G, Harrison M, Melichar B, Pezet D, Elekes A, Rock E, Lin C, Strauss L, O'Dwyer PJ. Phase 2 placebo-controlled, double-blind trial of dasatinib added to gemcitabine for patients with locally-advanced pancreatic cancer. Ann Oncol 2017; 28: 354-61

Meyer T, Fox R, Ma YT, Ross PJ, James MW, Sturgess R, Stubbs C, Stocken DD, Wall L, Watkinson A, Hacking N, Evans TRJ, Collins P, Hubner RA, Cunningham D, Primrose JN, Johnson PJ, Palmer DH. Sorafenib in combination with transarterial chemoembolisation in patients with unresectable hepatocellular carcinoma (TACE 2): a randomised placebo-controlled, double-blind, phase 3 trial. Lancet Gastroenterol Hepatol 2017; 2: 565-75

Vennin C, Chin VT, Warren SC, Lucas MC, Herrmann D, Magenau A, Melenec P, Walters SN, Del Monte-Nieto G, Conway JR, Nobis M, Allam AH, McCloy RA, Currey N, Pinese M, Boulghourjian A, Zaratzian A, Adam AA, Heu C, Nagrial AM et al. Transient tissue priming via ROCK inhibition uncouples pancreatic cancer progression, sensitivity to chemotherapy, and metastasis. Sci Transl Med 2017; 9: pii: eaai8504

Wilson RH, Evans TJ, Middleton MR, Molife LR, Spicer J, Dieras V, Roxburgh P, Giordano H, Jaw-Tsai S, Goble S, Plummer R. A phase I study of intravenous and oral rucaparib in combination with chemotherapy in patients with advanced solid tumours. Br J Cancer 2017; 116: 884-2

2016

Bailey P, Chang DK, Nones K, Johns AL, Patch AM, Gingras MC, Miller DK, Christ AN, Bruxner TJ, Quinn MC, Nourse C, Murtaugh LC, Harliwong I, Idrisoglu S, Manning S, Nourbakhsh E, Wani S, Fink L, Holmes O, Chin V et al. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature 531: 47-52, 2016

Driscoll DR, Karim SA, Sano M, Gay DM, Jacob W, Yu J, Mizukami Y, Gopinathan A, Jodrell DI, Evans TR, Bardeesy N, Hall MN, Quattrochi BJ, Klimstra DS, Barry ST, Sansom OJ, Lewis BC, Morton JP. mTORC2 signaling drives the development and progression of pancreatic cancer. Cancer Res 76: 6911-23, 2016

Graham JS, Boyd K, Coxon FY, Wall LR, Eatock MM, Maughan TS, Highley M, Soulis E, Harden S, Butzberger-Zimmerli P, Evans TR. A phase II study of capecitabine and oxaliplatin combination chemotherapy in patients with inoperable adenocarcinoma of the gall bladder or biliary tract. BMC Res Notes 9: 161, 2016

Guest RV, Boulter L, Dwyer BJ, Kendall TJ, Man TY, Minnis-Lyons SE, Lu WY, Robson AJ, Gonzalez SF, Raven A, Wojtacha D, Morton JP, Komuta M, Roskams T, Wigmore SJ, Sansom OJ, Forbes SJ. Notch3 drives development and progression of cholangiocarcinoma. Proc Natl Acad Sci USA 113: 12250-5, 2016

Jamieson D, Griffin MJ, Sludden J, Drew Y, Cresti N, Swales K, Merriman M, Allen R, Bevan P, Buerkle M, Mala C, Coyle V, Rodgers L, Dean E, Greystoke A, Banerji U, Wilson RH, Evans TR, Anthoney A, Ranson M, Boddy AV, Plummer R. A phase I pharmacokinetic and pharmacodynamic study of the oral mitogen-activated protein kinase kinase (MEK) inhibitor, WX-554, in patients with advanced solid tumours. Eur J Cancer 68: 1-10, 2016

Milojkovic Kerklaan B, Slater S, Flynn M, Greystoke A, Witteveen PO, Megui-Roelvink M, de Vos F, Dean E, Reyderman L, Ottesen L, Ranson M, Lolkema MP, Plummer R, Kristeleit R, Evans TR, Schellens JH. A phase I, dose escalation, pharmacodynamic, pharmacokinetic, and food-effect study of alpha2 integrin inhibitor E7820 in patients with advanced solid tumors. Invest New Drugs 34: 329-37, 2016

Propper D, Jones K, Anthoney DA, Mansoor W, Ford D, Eatock M, Agarwal R, Inatani M, Saito T, Abe M, Evans TR. Phase II study of TP300 in patients with advanced gastric or gastro-oesophageal junction adenocarcinoma. BMC Cancer 16: 779, 2016

Soria JC, Gan HK, Blagden SP, Plummer R, Arkenau HT, Ranson M, Evans TR, Zalcman G, Bahleda R, Hollebecque A, Lemech C, Dean E, Brown J, Gibson D, Peddareddigari V, Murray S, Nebot N, Mazumdar J, Swartz L, Auger KR Fleming RA, Singh R, Millward M. A phase I, pharmacokinetic and pharmacodynamic study of GSK2256098, a focal adhesion kinase inhibitor, in patients with advanced solid tumors. Ann Oncol 27: 2268-74, 2016

Steele CW, Karim SA, Leach JD, Bailey P, Upstill-Goddard R, Rishi L, Foth M, Bryson S, McDaid K, Wilson Z, Eberlein C, Candido JB, Clarke M, Nixon C, Connelly J, Jamieson N, Carter CR, Balkwill F, Chang DK, Evans TR, Strathdee D, Biankin AV, Nibbs RJ, Barry ST, Sansom OJ, Morton JP. CXCR2 inhibition profoundly suppresses metastases and augments immunotherapy in pancreatic ductal adenocarcinoma. Cancer Cell 29: 832-45, 2016

Zhu AX, Kang YK, Rosmorduc O, Evans TR, Santoro A, Ross P, Gane E, Vogel A, Jeffers M, Meinhardt G, Pena CE. Biomarker analyses of clinical outcomes in patients with advanced hepatocellular carcinoma treated with sorafenib with or without erlotinib in the SEARCH trial. Clin Cancer Res 22: 4870-9, 2016

Other Publications
Aparicio T, Zaanan A, Mary F, Afchain P, Manfredi S, Evans TR. Small bowel adenocarcinoma. Gastroenterol Clin North Am 45: 447-57, 2016

Bilsland AE, Spiliopoulou P, Evans TR. Virotherapy: Cancer gene therapy at last? F1000Res 2016 Aug 30;5. pii: F1000 Faculty Rev-2105. doi: 10.12688/f1000research.8211.1. eCollection 2016.

2015

Dikovskaya D, Cole JJ, Mason SM, Nixon C, Karim SA, McGarry L, Clark W, Hewitt RN, Sammons MA, Zhu J, Athineos D, Leach JD, Marchesi F, van Tuyn J, Tait SW, Brock C, Morton JP, Wu H, Berger SL, Blyth K, Adams PD. Mitotic Stress Is an Integral Part of the Oncogene-Induced Senescence Program that Promotes Multinucleation and Cell Cycle Arrest. Cell Rep 12: 1483-96, 2015

Faller WJ, Jackson TJ, Knight JR, Ridgway RA, Jamieson T, Karim SA, Jones C, Radulescu S, Huels DJ, Myant KB, Dudek KM, Casey HA, Scopelliti A, Cordero JB, Vidal M, Pende M, Ryazanov AG, Sonenberg N, Meyuhas O, Hall MN, Bushell M, Willis AE, Sansom OJ. mTORC1-mediated translational elongation limits intestinal tumour initiation and growth. Nature 517: 497-500, 2015

Hartmann D, von Figura G, Song Z, Harden S, Scott LC, Evans TR, Rudolph KL, Bilsland AE, Keith WN. Plasma N-acetyl-glucosaminidase in advanced gastro-intestinal adenocarcinoma correlates with age, stage and outcome. Future Oncol 11: 193-203, 2015

Miller BW, Morton JP, Pinese M, Saturno G, Jamieson NB, McGhee E, Timpson P, Leach J, McGarry L, Shanks E, Bailey P, Chang D, Oien K, Karim S, Au A, Steele C, Carter CR, McKay C, Anderson K, Evans TR, Marais R, Springer C, Biankin A, Erler JT, Sansom OJ. Targeting the LOX/hypoxia axis reverses many of the features that make pancreatic cancer deadly: inhibition of LOX abrogates metastasis and enhances drug efficacy. EMBO Mol Med 7: 1063-76, 2015

Puzanov I, Lindsay CR, Goff L, Sosman J, Gilbert J, Berlin J, Poondru S, Simantov R, Gedrich R, Stephens A, Chan E, Evans TRJ. A Phase I Study of Continuous Oral Dosing of OSI-906, a Dual Inhibitor of Insulin-Like Growth Factor-1 and Insulin Receptors in Patients with Advanced Solid Tumors. Clinical Cancer Research 21: 701-711, 2015

Steele CW, Karim SA, Foth M, Rishi L, Leach JD, Porter RJ, Nixon C, Jeffry Evans TR, Carter CR, Nibbs RJ, Sansom OJ, Morton JP. CXCR2 inhibition suppresses acute and chronic pancreatic inflammation in mice. J Pathol 237: 85-97, 2015

Venugopal B, Awada A, Evans TR, Dueland S, Hendlisz A, Rasch W, Hernes K, Hagen S, Aamdal S. A first-in-human phase I and pharmacokinetic study of CP-4126 (CO-101), a nucleoside analogue, in patients with advanced solid tumours. Cancer Chemother Pharmacol 76: 785-92, 2015

Zhu AX, Rosmorduc O, Evans TRJ, Ross P, Santoro A, Carrilho FJ, Bruix J, Qin S, Thuluvath PJ, Llovet JM, Leberre M-A, Jensen M, Meinhardt G, Kang Y-K. A Phase III, Randomized, Double-Blind, Placebo-Controlled Trial of Sorafenib plus Erlotinib in Patients with Advanced Hepatocellular Carcinoma. Journal of Clinical Oncology 33: 559-566, 2015

Evans TRJ. Upper Gastrointestinal Cancer. In: Oxford Handbook of Oncology, 4th Edition (eds: Cassidy J, Bissett D, Spence RAJ, Payne M, Morris-Stiff G). Oxford University Press, Oxford, UK, 2015; 317-380

Gopinathan A, Morton JP, Jodrell DI, Sansom OJ. GEMMs as preclinical models for testing pancreatic cancer therapies. Dis Model Mech 2015; 8: 1185-200

2014

Ali A, Brown V, Denley S, Jamieson NB, Morton JP, Nixon C, Graham JS, Sansom OJ, Carter CR, McKay CJ, Duthie FR, Oien KA. Expression of KOC, S100P, mesothelin and MUC1 in pancreatico-biliary adenocarcinomas: development and utility of a potential diagnostic immunohistochemistry panel. BMC Clin Pathol 2014; 14: 35

Arjonen A, Kaukonen R, Mattila E, Rouhi P, Hognas G, Sihto H, Miller BW, Morton JP, Bucher E, Taimen P, Virtakoivu R, Cao Y, Sansom OJ, Joensuu H, Ivaska J. Mutant p53-associated myosin-X upregulation promotes breast cancer invasion and metastasis. J Clin Invest 2014; 124: 1069-82

Cassier PA, Polivka V, Judson I, Soria JC, Penel N, Marsoni S, Verweij J, Schellens JH, Morales-Barrera R, Schoffski P, Voest EE, Gomez-Roca C, Evans TR, Plummer R, Gallerani E, Kaye SB, Olmos D. Outcome of patients with sarcoma and other mesenchymal tumours participating in phase I trials: a subset analysis of a European Phase I database. Ann Oncol 2014; 25: 1222-8

Faller WJ, Jackson TJ, Knight JR, Ridgway RA, Jamieson T, Karim SA, Jones C, Radulescu S, Huels DJ, Myant KB, Dudek KM, Casey HA, Scopelliti A, Cordero JB, Vidal M, Pende M, Ryazanov AG, Sonenberg N, Meyuhas O, Hall MN, Bushell M, Willis AE, Sansom OJ. mTORC1-mediated translational elongation limits intestinal tumour initiation and growth. Nature 2015; 517: 497-500, doi: 10.1038/nature13896. Epub 2014 Nov 5

Hamilton G, Abraham AG, Morton J, Sampson O, Pefani DE, Khoronenkova S, Grawenda A, Papaspyropoulos A, Jamieson N, McKay C, Sansom O, Dianov GL, O'Neill E. AKT regulates NPM dependent ARF localization and p53mut stability in tumors. Oncotarget 2014; 5: 6142-67

Herrmann D, Conway JR, Vennin C, Magenau A, Hughes WE, Morton JP, Timpson P. Three-dimensional cancer models mimic cell-matrix interactions in the tumour microenvironment. Carcinogenesis 2014; 35: 1671-9

Johnsson AK, Dai Y, Nobis M, Baker MJ, McGhee EJ, Walker S, Schwarz JP, Kadir S, Morton JP, Myant KB, Huels DJ, Segonds-Pichon A, Sansom OJ, Anderson KI, Timpson P, Welch HC. The Rac-FRET mouse reveals tight spatiotemporal control of Rac activity in primary cells and tissues. Cell Rep 2014; 6: 1153-64

Li A, Morton JP, Ma Y, Karim SA, Zhou Y, Faller WJ, Woodham EF, Morris HT, Stevenson RP, Juin A, Jamieson NB, MacKay CJ, Carter CR, Leung HY, Yamashiro S, Blyth K, Sansom OJ, Machesky LM. Fascin is regulated by slug, promotes progression of pancreatic cancer in mice, and is associated with patient outcomes. Gastroenterology 2014; 146: 1386-96 e1-17

Middleton G, Silcocks P, Cox T, Valle J, Wadsley J, Propper D, Coxon F, Ross P, Madhusudan S, Roques T, Cunningham D, Falk S, Wadd N, Harrison M, Corrie P, Iveson T, Robinson A, McAdam K, Eatock M, Evans J, Archer C, Hickish T, Garcia-Alonso A, Nicolson M, Steward W, Anthoney A, Greenhalf W, Shaw V, Costello E, Naisbitt D, Rawcliffe C, Nanson G, Neoptolemos J. Gemcitabine and capecitabine with or without telomerase peptide vaccine GV1001 in patients with locally advanced or metastatic pancreatic cancer (TeloVac): an open-label, randomised, phase 3 trial. Lancet Oncol 2014; 15: 829-40

Moreno Garcia V, Olmos D, Gomez-Roca C, Cassier P, Morales-Barrera R, Del Conte G, Gallerani E, Brunetto A, Schoffski P, Marsoni S, Schellens JH, Penel N, Voest E, Evans TR, Plummer ER, Wilson RH, Soria JC, Tabernero J, Verweij J, Kaye SB. Dose-response relationship in phase I clinical trials: A European drug development network (Eddn) collaboration study. Clin Cancer Res 2014; 20: 5663-71

Morran DC, Wu J, Jamieson NB, Mrowinska A, Kalna G, Karim SA, Au AY, Scarlett CJ, Chang DK, Pajak MZ, Oien KA, McKay CJ, Carter CR, Gillen G, Champion S, Pimlott SL, Anderson KI, Evans TR, Grimmond SM, Biankin AV, Sansom OJ, Morton JP. Targeting mTOR dependency in pancreatic cancer. Gut 2014; 63: 1481-9

Roxburgh P, Lumsden GR, Paul J, Harden S, Sweeting L, James A, Crellin A, Morrison R, Evans TR, McDonald AC. A phase I and pharmacokinetic study of capecitabine in combination with radiotherapy in patients with localised inoperable pancreatic cancer. Cancer Chemother Pharmacol 2014; 74: 131-9

Chang KD, Grimmond SM, Evans TRJ, Biankin AV. Mining the genomes of exceptional responders. Nature Reviews Cancer 2014; 14: 291-2

Lab Members

 

Evans Team 2012

Research

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Read more about the Research Groups working at the Beatson Institute.

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Seminars

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Find out more about our seminars including our Distinguished Seminar Programme.

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